This project will contribute to the elucidation of the control and mechanism of cytochrome P450-dependent processes which are involved in chemical carcinogenesis and in adrenal steroid biosynthesis. Biophysical and enzymological techniques will be applied to these problems. More specifically we will determine the factors which affect the relative rates of polycyclic hydrocarbon oxidation (activation to carcinogen) by cytochrome P450 and the enzymatic hydration (inactivation) of the epoxide intermediates in microsomes from various sources. The activation of a polycyclic hydrocarbon to carcinogenic activity by these preparations will be compared with the above enzyme characteristics. The mechanism by which ACTH activates the transport of cholesterol to adrenal mitochondria and the side chain cleavage of cholesterol by cytochrome P450 will be investigated. Research will concentrate on substantiating the hypothesis that ACTH activates steroid synthesis by the rapid ribosomal translation of a cholesterol transport protein. The properties of adrenal steroid hydroxylase activities will be studied in intact adrenal mitochondria and in purified preparations in relation to the involvement of different forms of cytochrome P450, which may under independent adrenal control. These results will be related to possible abnormalities of adrenal control which are observed, e.g. in hypertension and Cushings Syndrome.